We propose to analyze the genetic and epigenetic control of sensescence and death at the cellular level in Drosophila melanogaster. We will study the aging-like changes which occur in imaginal disc tissue cultured in vivo for long periods. These changes include loss of ability to differentiate normal structures, loss of growth control, in ability to metamorphose, acquisition of neoplastic properties, and degeneration. We intend to ascertain whether any of these changes in old disc cells can be reversed by direct cell contact and intercellular interaction with young cells. We also plan to study the developmental properties of other lines of imaginal disc tissue that appear to be virtually immortal and retain the ability to grow and differentiate after as long as 1800 cell generations and nine years of culture in vivo. We propose to analyze the control and function of localized cell death which occurs during the development of imaginal discs, by analyzing mutations which cause excessive cell death in particular areas. We also plan to use these muutations to induce cell death so that we can further analyze the resulting pattern deletions, duplications, triplications, and fusions. We shall mimic the effects of cell-death mutations by producing patches of cell death with a UV-laser microbeam, to define exactly the distribution of cell death necessary to give the observed phenotypes. We use Drosophila because of our conviction that the analysis of many aspects of cell aging and cell mortality will require the use of genetic mutations and genetic techniques such as somatic cell genetic analysis and clonal analysis which are readily available in this organism.